Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death of men in the US. Current therapies for advanced human prostatic adenocarcinoma are palliative - none are curative. Therefore, there remains an urgent need to understand the mechanisms driving progression and converting such knowledge into preventive/interventive modalities. The construction and phenotypic analysis of genetically engineered mouse strains are fundamental and integral requirements for all portions of this P01, including the analysis of signaling molecules in the pathogenesis of prostate cancer, the discovery and analysis of novel prostate cancer genes and their linked networks, and the validation and assessment of novel therapeutic targets and associated molecular biomarkers. To address these issues, the T.ransgenic Core will design and produce transgenic mouse strains and provide advice on their phenotypic characterization, design and produce knockout and knock-in mouse strains and provide advice on their phenotypic characterization and evaluate and implement new technologies for the construction of genetically engineered mice and derivative tissues. The mouse models generated will add to our understanding of prostate cancer initiation and progression. Furthermore, these models can be used directly in testing new treatments and assist in development of new methods of early detection.